Effect of pentoxifylline on graft function of renal transplant recipients complicated with chronic allograft nephropathy

Abstract

Chronic allograft nephropathy (CAN) is characterized by a progressive deterioration of renal function with various degrees ofproteinuria. Currently, there is no effective treatment despite the introduction of new generations of immunosuppressants. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses antiproteinuric effect and has been proved to be effective in treating several glomerular diseases. The purpose of the current study was to examine the effect of PTX on renal transplant patients with established CAN. Renal transplant recipients with biopsyproven CAN were recruited for the study. All the patients had been on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for more than 1 year and were on a triple immunosuppressive regimen including corticosteroid, calcineurine inhibitor and mycophenolate mofetil. PTX in a dose of 1,200 mg/day was administered for at least 6 months. The following parameters were assessed at baseline, the 3rd and the 6th month post treatment: systolic and diastolic blood pressure, number of anti-hypertension drugs, serum creatinine (sCr),estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion (U/P), urinary N-acetylglucosaminidase (NAG) and intracytoplasmic Thl/Th2 cytokines production of peripheral blood CD4+ cells. A total of 17 (11 male and 6 female) patients were enrolled in the study. The mean duration of follow-up post transplant was 10.6+/- 4.4 years. The baseline data of sCr, eGFR and U/P were 1.83+/-0.46 mg/dl, 38+/-8 ml/min and 2.65+/-2.15 g/day, respectively. Corresponding values at the 3rd and 6th month post treatment were 1.90+/-0.43 mg/dl (p = NS), 33+/-7 ml/min (p=NS), 2.13 +/-1.13 g/day (p < 0.05) and 2.03+/-0.64 mg/dl (p < 0.05), 32+/-10 ml/min (p < 0.05), 2.74 +/-0.93 g/day (p = NS), respectively. When individual data were analyzed, five cases (29.4%) showed a U/P significant reduction of more than 50% of baseline value, while in 10 cases (58.8%) the graft function remained either stable (9 cases) or improved (1 case) at the end of treatment. Urinary NAG was elevated at the 3rd month, but stabilized thereafter. The Thl/Th2 intracytoplasmic cytokine pattern of peripheral blood CD4+ cells showed a significant decrease of cells bearing TNF-alpha (15.0+/-14.4% vs 14.2+/-17.0%, p < 0.05) and cells bearing IL-10 (1.60 +/-1.23% vs 0.90+/-0.66%, p < 0.05) at the 3rd month. In this pilot study, PTX seemed to be temporarily effective in reducing proteinuria. The graft function was stabilized in more than half of patients at the end of follow-up.